PET Quantification of Tau Pathology in Human Brain with 11C-PBB3.

Abstract

Tau accumulation in the brain is a pathologic hallmark of Alzheimer disease and other tauopathies. Quantitative visualization of tau pathology in humans can be a powerful method as a diagnostic aid and for monitoring potential therapeutic interventions. We established methods of PET quantification of tau pathology with (11)C-PBB3 (2-((1E,3E)-4-(6-((11)C-methylamino)pyridin-3-yl)buta-1,3-dienyl) benzo[d]thiazol-6-ol), considering its radiometabolite entering the brain. Seven Alzheimer disease patients and 7 healthy subjects underwent dynamic (11)C-PBB3 PET scanning. Arterial blood was sampled to obtain the parent and metabolite input functions. Quantification of (11)C-PBB3 binding was performed using dual-input models that take the brain metabolite activity into consideration, traditional single-input models without such considerations, and the reference tissue model (MRTMO) and standardized uptake value ratio (SUVR). The cerebellar cortex was used as the reference tissue for all methods. The dual-input graphical models estimated binding parameter ([Formula: see text]) stably (∼0.36 in high-binding regions). The MRTMO [Formula: see text] matched the corresponding [Formula: see text] by the dual-input graphical model (r(2) = 1.00). SUVR minus 1 correlated well with MRTMO [Formula: see text] (r(2) > 0.97). However, BPND by the single-input models did not correlate with [Formula: see text] by the dual-input graphical model (r(2) = 0.04). The dual-input graphical model [Formula: see text] is consistent with the reference tissue [Formula: see text] and SUVR-1, suggesting that these parameters can accurately quantify binding of (11)C-PBB3 despite the entry of its radiometabolites into the brain.